Suicide gene therapy for mouse bladder cancer using HSV-tk/GCV system

Objective:To establish a suicide gene therapy system HSV-tk/GCV for bladder cancer,a treatment in vitro as well as in vivo and to test its efficacy.Methods:Mouse bladder cancer cell line (T739) was transfected with retroviral vector HSV-tk gene.The sensitivity of T739-TK cells to GCV was detected in vitro.In the mouse model of bladder tumor,T739 or T739-TK was implanted beneath the peritoneum of syngeneic mice.When tumors grew to the size of 0.5～0.8cm,intraperitoneal administration of GCV was carried out for 6 days.Changes of tumor size and survival rate of mice were observed.Results:RT-PCR showed that TK gene was transferred into the T739 cell and expressed successfully. In vitro,T739-TK cells became sensitive to low concentrations of GCV.In vivo studies showed similar result.Significant tumor inhibition was found in the T739-TK group after administration of GCV,and the survival time of mice was prolonged.Conclusion:Tumor cells expressing HSV-tk gene were eradicated by administration of GCV in vitro as well as in vivo.